Variant chr2-135638642-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001378107.1(R3HDM1):c.928A>C(p.Ile310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,610,556 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

R3HDM1
NM_001378107.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

R3HDM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018303633).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1 linkuse as main transcript	c.928A>C	p.Ile310Leu	missense_variant	12/27	ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1 linkuse as main transcript	c.928A>C	p.Ile310Leu	missense_variant	12/27		NM_001378107.1	A1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000474

AC:

119

AN:

251198

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000942

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00101

AC:

1468

AN:

1458402

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

684

AN XY:

725804

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.000440

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000779

Hom.:

Bravo

AF:

0.000453

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000519

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.0069

.;T;.;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

.;D;T;T;D

M_CAP

Benign

0.0024

MetaRNN

Benign

0.018

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.96

.;N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.15

N;N;N;.;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T;T;.;T

Sift4G

Benign

0.78

T;T;T;T;T

Polyphen

0.0

.;B;.;.;.

Vest4

0.18

MVP

0.34

MPC

0.24

ClinPred

0.027

GERP RS

4.3

Varity_R

0.065

gMVP

0.093

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over